Timing of oral anticoagulants initiation for atrial fibrillation after acute ischemic stroke: A systematic review and meta-analysis

Introduction: There is a longstanding clinical uncertainty regarding the optimal timing of initiating oral anticoagulants (OAC) for non-valvular atrial fibrillation following acute ischemic stroke. Current international recommendations are based on expert opinions, while significant diversity among clinicians is noted in everyday practice. Methods: We conducted an updated systematic review and meta-analysis including all available randomized-controlled clinical trials (RCTs) and observational cohort studies that investigated early versus later OAC-initiation for atrial fibrillation after acute ischemic stroke. The primary outcome was defined as the composite of ischemic and hemorrhagic events and mortality at follow-up. Secondary outcomes included the components of the composite outcome (ischemic stroke recurrence, intracranial hemorrhage, major bleeding, and all-cause mortality). Pooled estimates were calculated with random-effects model. Results: Nine studies (two RCTs and seven observational) were included comprising a total of 4946 patients with early OAC-initiation versus 4573 patients with later OAC-initiation following acute ischemic stroke. Early OAC-initiation was associated with reduced risk of the composite outcome (RR = 0.74; 95% CI:0.56–0.98; I2 = 46%) and ischemic stroke recurrence (RR = 0.64; 95% CI:0.43–0.95; I2 = 60%) compared to late OAC-initiation. Regarding safety outcomes, similar rates of intracranial hemorrhage (RR = 0.98; 95% CI:0.57–1.69; I2 = 21%), major bleeding (RR = 0.78; 95% CI:0.40–1.51; I2 = 0%), and mortality (RR = 0.94; 95% CI:0.61–1.45; I2 = 0%) were observed. There were no subgroup differences, when RCTs and observational studies were separately evaluated. Conclusions: Early OAC-initiation in acute ischemic stroke patients with non-valvular atrial fibrillation appears to have better efficacy and a similar safety profile compared to later OAC-initiation.